Objective To analyze the dynamic changes to disease activity,colonic inflammation,histopathology,and serum cytokine levels in mice with chronic ulcerative colitis(UC).Methods For UC induction,2.5％dextran sodium sulfate solution was provided ad libitum for 5 days,and to model remission,tap water was supplied for another 5 days in one induction cycle.Disease activity index(DAI),colon length,and pathological changes to colon tissue were determined.The levels of myeloperoxidase(MPO)in colon tissue and of cytokines such as IL-1 β in serum and colon were detected.Results During the three cycles,disease activity was aggravated and colon length shortened in mice during the induction periods,both of which were relieved during the remission periods.The blood appeared was observed in the stool was earlier in cycles 2 and 3.The number of mice with stool blood increased,and their body weight decreased by a small amount briefly,then recovered rapidly.The degree of histopathological damage to the colon and MPO content in cycles 1 and 3 increased in the induction periods and decreased in the remission periods,with the magnitude of change smaller than that of the change in DAI values;and they increased in the remission period of cycle 2.During induction,the spleen index and serum levels of IL-1β,IL-6,and IL-17A increased continuously and were higher than those in the control group at the end of the experiment.Levels of TNF-α were increased in the induction periods and decreased in the remission periods,and the trend in IL-10 change was similar to that of TNF-α.TGF-β content increased and then decreased and was higher than that in the control group at the end of cycle 3.The colon contents of IL-1β,IL-6,and IL-17A showed similar trends of increasing and then decreasing,but there was no significant change in colon TNF-α.The concentration of IL-10 decreased during the induction periods and increased during the remission periods.Conclusions During the induction of chronic UC in mice,the symptoms of hematochezia and systemic inflammatory reactions gradually increased,and the mice showed an increase in tolerance and ability to resist mortality,weight loss,and histopathological injury to the colon.The onset and remission of colonic histopathological damage lags behind symptomatic changes,and there is a gradual shift in colonic inflammation to a pattern dominated by polymorphonuclear neutrophils(PMN)activation.

Objective:To investigate the application of three-dimensional digital technique in customized ear framework fabrication for auricular reconstruction.Methods:From July 2018 to October 2019, the patients with microtia who underwent ear reconstruction in the Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University were enrolled. Each patient with unilateral microtia underwent auricular CT scan and preoperative analysis and ear framework design were carried out with Mimics software 18.0. The two-dimension(2D) ear films and three-dimension(3D) silicon models were produced by 1∶1 2D printing and 3D printing, respectively. Microtia reconstruction was performed according to the guide of the models, patients were followed up over a six-month period to evaluate the size, outline, height and auriculocephalic angle of the reconstructed ear. The satisfactory outcomes of the patients were scored according to a 5-point Likert scale.Results:A total of 15 patients were included in this study, including 11 males and 4 females, aged 8-27 years, with an average of 15.5 years old. All the 15 patients completed the surgical planning and ear reconstruction successfully, without major complications, such as hematomas, inflammation, skin necrosis and framework exposure. The costal cartilage frameworks were very similar to the printed 3D models in size and contour. Comparison between the two sides was made at six months postoperatively. The reconstructed ear was much the same as that of contralateral side, and all patients were satisfied with their reconstructed ear outcomes with average score of 4.4.Conclusions:With the application of digital technique for pre-surgical planning in microtia reconstruction patients, ear templates were produced from 2D to 3D, and the correction of microtia was changed from standard auricular reconstruction to personalized auricular reconstruction, with a great improvement of the precision in ear framework fabrication.

Objective:To investigate the application of three-dimensional digital technique in customized ear framework fabrication for auricular reconstruction.Methods:From July 2018 to October 2019, the patients with microtia who underwent ear reconstruction in the Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University were enrolled. Each patient with unilateral microtia underwent auricular CT scan and preoperative analysis and ear framework design were carried out with Mimics software 18.0. The two-dimension(2D) ear films and three-dimension(3D) silicon models were produced by 1∶1 2D printing and 3D printing, respectively. Microtia reconstruction was performed according to the guide of the models, patients were followed up over a six-month period to evaluate the size, outline, height and auriculocephalic angle of the reconstructed ear. The satisfactory outcomes of the patients were scored according to a 5-point Likert scale.Results:A total of 15 patients were included in this study, including 11 males and 4 females, aged 8-27 years, with an average of 15.5 years old. All the 15 patients completed the surgical planning and ear reconstruction successfully, without major complications, such as hematomas, inflammation, skin necrosis and framework exposure. The costal cartilage frameworks were very similar to the printed 3D models in size and contour. Comparison between the two sides was made at six months postoperatively. The reconstructed ear was much the same as that of contralateral side, and all patients were satisfied with their reconstructed ear outcomes with average score of 4.4.Conclusions:With the application of digital technique for pre-surgical planning in microtia reconstruction patients, ear templates were produced from 2D to 3D, and the correction of microtia was changed from standard auricular reconstruction to personalized auricular reconstruction, with a great improvement of the precision in ear framework fabrication.

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

Objective To explore the characterization of thyroid stimulating hormone receptor(TSHR) gene mutational spectrum in children with hyperthyroidism from Guangzhou. Methods Ninety children were diagnosed with hyperthyroidism from July 2009 to July 2014 in our institute. Their median age at diagnosis was(7.5± 3.4) years, and there were 28 males and 62 females. Mutational analysis were performed by performing polymerase chain reaction (PCR) and DNA direct sequencing of exon 10 of TSHR gene. TSHR gene mutations from 50 unrelated healthy children were served as controls. The correlation between TSHR gene and hyperthyroidism in children was explored. Results A total of 3 mutations were identified in ninety children who were diagnosed with hyperthyroidism, one synonymous mutations(p.V614V), and two missense mutations( p. R707W and p. D727E). Mutation of p. V614V do not change amino acid and do not influence the structure and function of TSHR, no pathogenicity. p.R707W is a SNP associated with human cancers. The frequency of C allele of the D727E in children with hyperthyroidism was 86.7%, while 55.0% in the controls, significant different between the children with hyperthyroidism and the controls( P＜0. 01). In this study, a very high association between the D727E SNP and hyperthyroidism ( OR=18. 86, P＜0. 01) was found. Conclusion Three different mutations of TSHR gene exon 10 were identified in 90 children with hyperthyroidism, (c.1842A＞G,p.V614V、c.2119C＞T,p.R707W、c.2181G＞C,p.D727E), there were association between p.D727E and hyperthyroidism, nor p. V614V and p. R707W. Finally, p. D727E may be correlated with hyperthyroidism in children.

Objective To understand the clinical and molecular characteristics of children with Prader-Willi syndrome (PWS) in South China.Methods Clinical and molecular data of children diagnosed as PWS by Methylation-specific PCR(MS-PCR) and/or Array Comparative Genomic Hybridization(Array-CGH)in Guangzhou Women and Children's Medical Center from November 2012 to November 2014 were analyzed.Results A total of 27 children diagnosed as PWS were included in this study,including 21 cases diagnosed by Array Comparative Genomic Hybridization (Array-CGH) and 13 cases diagnosed by methylation-specific PC R (MS-PCR).Within the 27 cases,13 cases were male(48.1％) and 14 cases were female(51.9％).The age on diagnosis was from 16 days to 16 years old.MS-PCR was performed in 13 cases,7 cases of them also performed Array-CGH,both of them showed a 174 bp fragment from the methylated allele and a 100 bp fragment from the unmethylated allele.Array-CGH analysis was performed in 21 cases,paternal deletion in 18 cases and mean interstitial deletions measure (5.48 ± 0.51) Mb in size,paternal duplication in 2 cases,loss of heterozygosity measure approximately 79.58 Mb in 1 case.Eighteen simple chromosome deletion cases were divided into 6 Del Ⅰ and 12 Del Ⅱ according to the location of Array-CGH and query the database to DECIPHER(Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources).The major phenotype included central hypotonia and feeding difficulty in all cases (100.0％),hypogonadism in 25 cases (92.6％),weak crying in 22 cases(81.5％),and hypopigmentation in 22 cases(81.5％).Fourteen cases beyond 1 year old had varied degrees of development disability and behavioral and psychiatric disturbance:speech articulation defects in 13 cases(92.9％),hyperphagia and weight gain too fast in 13 cases(92.9％) when they were between 1 to 6 years old[(2.80 ± 1.32) years old],and obesity in 12 cases (85.7％).Conclusions For PWS children in South China,there is no statistically significant difference in the clinical manifestation between Del Ⅰ and Del Ⅱ.PWS children in South China have typical clinical characteristics,which can be used as a further screening indication to implement molecular diagnostics.

The cause of hyperthyroidism is still not clear.Thyroid stimulating hormone receptor(TSHR) gene is one of the hot topic genes in the etiology of hyperthyroidism.In this review paper,the progress of correlation between TSHR gene and hyperthyroidism was summarized.Results suggested that TSHR gene germline mutations could cause familial non-autoimmune autosomal dominant hyperthyroidism and persistent sporadic congenital non-autoimmune hyperthyroidism.In addition,TSHR gene mutation may also undermine the stability of the TSHR and then become the autoantigens to make producing TSHR antibodies.Which can stimulate thyroid follicular to secrete excessive thyroid hormone and then cause Graves' disease.However,the relationship between TSHR gene and the pathogenesis of Graves' disease still needs further study.

Objective To investigate the clinical efficacy and adverse events of methimazole ( MMI ) treatment for children with hyperthyroidism, and to identify the predictors of remission and relapse. Methods A total of379children(260girlsand119boys)diagnosedwithhyperthyroidismandtreatedbyMMIinGuangzhouWomenand Children's Medical Center from March, 2004 to July, 2014 were retrospectively analyzed. The average age at diagnosiswas(9.3±2.3)years(range2.0~15.9years). Results AftertreatmentwithMMIfor3and6months, the thyroid functions of 96. 3%(365/379) and 98. 9%(375/379) patients returned to normal, respectively. By the end of this study, 256(67. 5%) patients continued to use MMI treatment and 44 patients(11. 6%) dropped out. 79 patients(20. 8%) achieved remission, 35 patients (44. 3%) of whom experienced a later relapse. Children who achieved constant remission had significantly lower FT3 and FT4 levels at diagnosis compared with the relapsed children(P<0. 05 or P<0. 01). It was more likely to remain long-term remission for children turned to be euthyroid within 3 months after initiating MMI treatment(P<0. 05). The relieved patients with family history of thyroid diseases weremorelikelytoberelapsed(P<0.05). Therewerenosignificantdifferencesinage,gender,exophthalmos, initial goiter size, thyroid peroxidase autoantibody, and thyroglobulin antibody levels between the relieved and relapsed patients. The overall incidence of adverse events associated with MMI was 27. 7%, mainly elevated alanine aminotransferase, bilirubin, and neutropenia. Most(66. 7%) of adverse events occurred within the first three months of MMI treatment. Conclusion MMI has a good effect on pediatric hyperthyroidism, with low remission and high relapse rate. The low thyroid hormone concentrations at diagnosis and normalization of thyroid function within three months seem to be useful predictors of remission. Vigilance is needed concerning MMI-associated adverse events throughout the MMI treatment period, especially during the first trimester of MMI initiation.

EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation, metastasis and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer. 3-Deazaneplanocin A (DZNep), as an EZH2 inhibitor, can suppress cancer cell growth. However, the anti-cancer role of DZNep in colon cancer cells has been rarely studied. In this study, we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis. The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.

OBJECTIVEMucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disease caused by a deficiency of arylsulfatase B(ARSB), which is required in the degradation of dermatan sulfate and chondroitin sulfate. The deficiency of ARSB leads to an accumulation of dermatan sulfate and chondroitin sulfate in lysosomes and gross excretion in the urine.Few articles about clinical study and ARSB gene mutation analysis of Chinese MPS VI patients were published. This study aimed to explore the clinical features and characteristics of ARSB gene in Chinese children with MPS VI.

METHODThirteen children were diagnosed as MPS VI by ARSB enzyme activity determination during the period from 2009 to 2013. Their clinical features, radiological findings and urine glycosaminoglycan (GAG) levels were retrospectively reviewed. Direct sequencing was used to identify any mutation in the ARSB gene.

RESULTThirteen children were diagnosed at the average age of (3.9 ± 2.2) years with 6 male and 7 female. All of these children presented with severe form and onset at an early age of (1.5 ± 0.8) years.Other clinical features included coarse facies, short stature, skeleton deformity, corneal clouding, hepatosplenomegaly with normal intelligence. The radiological findings in all children were characteristic of dysostosis multiplex, like abnormal development of vertebral bodies of the spine, campylorrhachia and paddle-shaped widened ribs. The MRI in case 2 showed cervical cord compression and multiple cysts degeneration in the corona radiate, cella lateralis and callosum.High urine GAG levels were detected, (307.10 ± 112.14) mg/L (Normally below 70 mg/L) and (722.28 ± 245.68) µg/mg creatinine. The ARSB enzyme activity in leukocytes was low, (13.29 ± 6.22) nmol/(mg×h) [Normal range (47-169) nmol/(mg×h)] by fluorogenic assay and (0.24 ± 0.18) U/g [Normal range (1.01-11.47) U/g] by colorimetric assay. A total of 11 mutations were identified by molecular analysis, including seven previously reported mutations (p.L72R, p.G167R, p.G303E, p.F399L, p. T442M, p.Y255X and p.R327X) and four novel mutations (p.Y175D, p.S403X, p.S464X and large deletion including ex. 2, 3). The c.1197C>G (p.F399L) mutation was the most common mutation in this study (31%).

CONCLUSIONThe severe form of MPS VI is characterized by early onset and rapid illness progression. Both the radiological findings and increased urine GAG are important clues to diagnose MPS VI.Large decrease or absence of ARSB activity is diagnostic for MPS VI.Four novel mutations of ARSB gene were identified. The reported mutation c.1197C>G (p.F399L) was the hot-spot mutation in this study.

Bone and Bones ; diagnostic imaging ; pathology ; Brain ; pathology ; Child ; Child, Preschool ; Exons ; genetics ; Female ; Glycosaminoglycans ; urine ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Mucopolysaccharidosis VI ; diagnosis ; enzymology ; genetics ; Mutation ; N-Acetylgalactosamine-4-Sulfatase ; genetics ; metabolism ; Polymerase Chain Reaction ; Radiography ; Retrospective Studies ; Sequence Analysis, DNA